Ga-68 PET. John Buscombe

Ga-68 PET

Introduction

n  Ga-68 a new radionuclide

n  PET based

n  Chemistry can be difficult

n  Used primarily with DOTATATE

In-111 octreotide v F-18 FDG

in NET patients the ying and

yang of cancer

F-18 FDG In-111 octreotide

PET-CT showing multiple sites of F-18 FDG

uptake in nodes involved with disseminated pancreatic non-secreting NET

How can we improve SRS

n  We can improve affinity of the peptide

for the tumour site

n  octreoTATE >octreoTOC >octreotide

>lanreotide

n  Can we find a radioisotope with PET

capabilities (F-18 not a stable labeller of peptides).

Affinities

1

2

3

4

5 SSR

What is Ga-68 DOTATATE

n  Ga-68

–  Short lived daughter of Ge-68

–  Therefore generator produced

–  Half life 68 minutes

–  Positron emitter

n  DOTA

–  Linker molecule

n  TATE

–  Alcoholised somatostatin analogue

Development of Ga-68

DOTATATE

n  Ge-68/Ga-68 used for AC for PET

before CT based systems

n  Ga-68 been used in-vivo since 1983

n  Ga-68 IDA for PET Hidas

n  Ga-68 EDTA for PET renograms

n  Ga-68 mercapatobenzyl-amine for

cardiacs

Ge-68/Ga68 generator

n  Ge-68 generator 127 day half life

n  Made in Russia and ?South Africa

n  Can be eluted 1-2 times a day

n  First eluate up to 500GBq

n  Ge-68 breakthrough low (<0.02%)

n  Can be eluted in 12 minutes

n  Needs fast chemistry (automated

iThemba generator

n  Made in South

Africa

n  Still not in routine

production

n  About 10cm high

and 6cm in diameter

n  Still need to get

DOTATATE/

Ga-68 somatostatins

n  Since 2001 Ga-68 somatostatins used

in NET and brain primaries

n  Work centred on Hanover, Heidelburg

and Basel

n  84 patients imaged with Ga-68

DOTATATE and In-111 pentetreotide JNM 2007 from Innsbruck

n  Sensitivity 96% compared with 65%

Comparison of In-111 pentetreotide

with Ga-68 Dotatate PET /computed

tomography uptake patterns in

patients with Neuroendocrine tumours

R Srirajaskanthan, J Bomanji, A-M Quigley I Kayani, ME Caplin, JNM 2010

Royal Free Hospital and University College London Hospital, London UK.

Background

n  Ga-68 Dotatate is a relatively new PET tracer with

affinity for SSR2

n  Routine In-111 Octreotide (pentetreotide, SSR 2,5

and 3) scans performed as general work-up in our NET patients and many also have Ga-68 Dotatate PET/CT

n  Impression of more lesions on Ga-68 Dotatate

Aim

n  Compare In-111 Octreotide

(pentetreotide) with Ga-68 DOTATATE PET/CT uptake patterns in patients

with histologically confirmed neuroendocrine tumours

n  Determine whether uptake related to

Methods

n  Images from the two studies were retrospectively

compared lesion by lesion (both scans performed within 4 month window)

n  categorized accordingly

both studies positive, Ga-68 more lesions both studies positive, In-111 more lesions both studies similar lesions

pos Ga-68, negative In-111 pos In-111, neg Ga-68

both studies negative

Results

n  44 patients included

17 foregut 21 midgut

1 hindgut

3 unknown origin 2 other NET types

n  1 patient no SPECT performed : technical problem

RESULTS

SCAN APPEARANCE _N=44

both studies positive, Ga-68 more lesions ₁₈ both studies positive, In-111 more

lesions 1

both studies similar lesions ₇

pos Ga-68, negative In-111 ₁₁

pos In-111, neg Ga-68 ₀

Ga-68 PET/CT more lesions than

In-111 Oct

In fact 11% of

patients negative of In-111 octreotide are positive on Ga-68 DOTATATE

In-111 Oct WB

SPECT Ga-68 PET/CT

Ga-68 PET/CT pos In-111 Oct neg

In-111 Oct Ga-68 PET

Ga-68 PET/CT more lesions than In-111 Oct

Ga-68 PET In-111 Oct

In-111 Oct more lesions than Ga-68 PET/CT

Ga-68 PET In-111 Oct

Ga-68 DOTATATE

n  Normally expect uptake of Ga-68

DOTATATE OR F-18 FDG

n  However in 18 pts Kayani et al (JNM

2005) showed uptake of both

n  However more false positives with

F-18 FDG

n  Recommend use of Ga-68 DOTATATE

Ga-68 DOTATATE

n  Compared with FDG in MTC

n  Conry et al EJNM 2010

n  18 patients with raised calcitonin

– 13 positive with Ga-68 DOTATATE

– 15 postive with F-18 FDG

F-18 FDG measure metabolism and

Ga-68 DOTATATE receptor activity

Same patient imaged with both tracers. NET

unknown origin

Biopsy of F-18 FDG lesion shows Ki67 of >10%.

Biopsy of Ga-68 DOTATATE positive lesion Ki-67 1% Patient responding to FCIST

Midgut NET

New lung lesion:

Other Ga-68 derivatives

n  Ga-68 DOTANOC higher affinity for

SSR 3 and 5 expressed in fore-gut tumours Wild D et al

n  Ga-68 minigastrin pancreatic tumours

Van Googenburg Innsbruck

n  Ga-68 DOTAVAP-PEG V2 looking at

vascular adhesion at sites of

Ga-68 PSMA SBAH

Conclusions

n  Imaging has different roles depending

on what the tumour is doing

n  May be used for diagnosis

n  For staging and restaging

n  Deciding best form of treatment

n  Monitoring the effect of treatment